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Infectious Disease: Unit 2 > Sepsis > Flashcards

Flashcards in Sepsis Deck (16):
1

Sepsis definition

  • SIRS + infection
    • Temp >38C or <36C
    • HR > 90
    • RR > 20
    • PaCO2 <32

2

Sepsis/SIRS Septic shock

  1. SIRS = Temp: >38,<36 HR: >90 RR: >20, PaCO2<32
  2. + infection
  3. + organ dysfxn OR decreased perfusion/BP
    1. BP < 90 (or decreased by 40 from baseline)
  4. + decreased perfusion/BP despite resuscitation

3

Multiple organ dysfxn syndrome definition/criteria

  1. SIRS = Temp: >38,<36 HR: >90 RR: >20, PaCO2<32
  2. + infection ==> sepsis
  3. + organ dysfxn OR decreased perfusion/BP
  4. BP < 90 (or decreased by 40 from baseline)
  5. + decreased perfusion/BP despite resuscitation ==> septic shock
  6. + >=2 organ dysfxns requiring intervention ==> MODS

4

Organ dysfxn variables

  • Pulmonary = PaO2 : FiO2 <300
  • Renal
    • • Oliguria (UOP <0.5 ml/kg/hr)
    • • Se creatinine ↑>0.5 mg/dl
  • Hemat
    • • Coagulation abnormalities (INR >1.5; or aPTT >60 sec)
    • • Thrombocytopenia (Platelets <100k/mm3)
  • GI
    • • Paralytic ileus  
  • • Hyperbilirubinemia

5

Common causes/infections ==> sepsis

  1. Respiratory
  2. Genitourinary
  3. Wound/soft tissue
  4. abdominal

6

Types of organisms that causes sepsis

  1. gram-negative bacteria positive (60%)
  2. gram-positive bacertia positive (45%)

7

Highest mortality infection sites ==> sepsis

  1. Endocarditis
  2. Respiratory
  3. CNS

8

Risks for developing sepsis

  •  male sex
  • race: non-caucasian > caucasians
  • age (older)
  • comorbid medical conditions
    • between 6 and 30% of all intensive care unit (ICU) patients
  • alcohol abuse
  • lower socioeconomic status
  •  

9

Early cellular and molecular events during infection

  1. vasodilation and endothelial activation
  2. leukocyte recruitment and activation
  3. coagulation and NET formation

10

General path ==> sepsis

  1. local growth of pathogen w/low load of bacteria and inflammation
    1. effective immune response ==> contained infection, bacterial clearance, limited immune system activation, no organ fail
  2. innefective immune response ==> systemic bacterial dissemination
    1. systemically elevated cytokines
    2. multiple organ failure

11

Energy metabolism crisis in sepsis

  • Mitochondrial “dysoxia” or Cytopathic Hypoxia: Oxygen utilization (VO2) by the mitochondria is dysfunctional, but oxygen delivery (DO2) is preserved!
  • • Impaired pyruvate delivery
  • • Inhibition of Krebs cycle or electron transport chain
  • • Activation of poly(ADPribosyl) polymerase (PARP)
  • • Failed maintenance of the transmitochondrial membrane gradient with uncoupling of ATP synthase.

12

Characteristics of immune fxn in early and late sepsis (+consequences)

  • Early sepsis
    • TH1 cytokines and chemokines ==> hyperinflammatory response
    • ==> death w/acute organ dysfxn due to cytokine storm
  • Late sepsis
    • Apoptotis depletion of immune cells + TH2 responses ==> hypoinflammatory response
    • ==> death due to primary infection or development of secondary infection

13

(General) characteristics of surviving sepsis caampaign

  • RESUSCITATION BUNDLE
  • Start immediately complete within 3 hours
  • “Surviving Sepsis v2014”
  • Multimodal treatment for Severe HCAP, Septic Shock/MODS

14

Steps in the surviving sepsis resuscitation bundle

  •  1. Routine Sepsis Screening (1C)
  • 2. Blood & Respiratory Cx
  • 3. Broad Spectrum Abx-1 hr
  • 4. IV N/S 30mL/kg in 1st 2 hr
    • • Add albumin (2B)
  • 5. Normalize Serum Lactate (2C)
  • 6. Vasopressors:
    • • Norepinephrine 10μg/min (1B)
    • • Epinephrine added or alternative (1C)
    • • DOPA only in selected (2C)
      • • ?Vasopressin:
      • • Dobutamine:
  • 7. Quantitative Resuscitation Targets (Shock, Lactate>4)
    • • MAP≥65 mm Hg
    • UOP ≥ 0.5 mL/kg/hr

15

Sepsis Recognition: TAKE HOME POINTS!

  •  • Severe sepsis is a very common, life-threatening complication in hospitalized patients
  • • The diagnosis may be subtle
  • • Evaluate for trends over time (i.e. VS, UO, CNS)
  • • For prompt recognition, consider severe sepsis as the cause of any new unexplained symptoms, signs, or laboratory abnormalities, even when you don’t suspect infection
  • • Always assess the severity of sepsis
  • • Even when illness seems mild, by VS/appearance, ALWAYS √ lactate and screen for organ dysfunction 

16

Why do novel therapies for sepsis (nearly all) fail in clinical trial?

  • • Inadequate phenotyping, prevention and delivery of care
    • • No reliable biomarkers for risk & disease progression
    • • No personalized approaches to risk stratification
    • • Suboptimal standardization for 1resusc.
  • Inadequate molecular mechanistic understanding
    • • Activated protein C: ePCR vs anticoagulant properties
    • • Antibody blockade of single cytokines unsuccessful: TNF and IL-1β
  • • Ineffective therapeutic targeting:
    • • Late mediators - vascular leak and end organ damage
    • • Enhancing anti-inflammatory, anti-bacterial, and repair pathways •
    • Mitigating post-septic immunosuppression by immunostimulation